HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: A potential therapeutic target?

Salvatore Galdy, Angela Lamarca, Mairead Mcnamara, Richard Hubner, Chiara A. Cella, Nicola Fazio, Juan Valle

Research output: Contribution to journalArticlepeer-review


Background: HER2 overexpression and/or amplification have been reported as predictive markers for HER2-targeted therapy in breast and gastric cancer, whereas HER3 is emerging as a potential resistance factor. The aim of this study was to perform a systematic review and meta-analysis of the HER2 and HER3 over-expression and amplification in biliary tract cancers (BTCs).
Methods: An electronic search of MEDLINE, ASCO, ESMO and AACR was performed to identify studies reporting HER2 and/or HER3 membrane protein expression by immunohistochemistry (IHC) and/or gene amplification by in situ hybridization (ISH) in BTCs. Studies were classified as “high-quality” (HQ) if IHC overexpression was defined as presence of moderate/strong staining; or “low-quality” (LQ) where “any” expression was considered positive.
Results: Of 440 studies screened, 40 met the inclusion criteria. Globally, HER2 expression rate was 26.5% (95%-CI 18.9-34.1%). When HQ studies were analyzed (n=27 studies), extra-hepatic BTCs showed a higher HER2 overexpression rate compared to intrahepatic cholangiocarcinoma: 19.9% (95%-CI 12.8-27.1%) vs. 4.8% (95%-CI 0-14.5%), respectively; p-value 0.0049. HER2 amplification rate was higher in patients selected by HER2 overexpression compared to “unselected” patients: 57.6% (95%-CI 16.2-99%) vs. 17.9% (95%-CI 0.1- 35.4%), respectively; p-value 0.0072. HER3 overexpression (4/4 HQ studies) and amplification rates were 27.9% (95%-CI 9.7-46.1%) and 26.5% (one study), respectively.
Conclusions: Up to 20% of extrahepatic BTCs appear to be HER2 overexpressed; of these close to 60% appear to be HER2-amplified; while HER3 is overexpressed or amplified in about 25% of patients. Clinical relevance for targeted therapy should be tested in prospective clinical trials.
Original languageEnglish
Pages (from-to)141-157
Number of pages17
JournalCancer and Metastasis Reviews
Issue number1
Early online date15 Dec 2016
Publication statusPublished - Mar 2017

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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